Skeletal muscle is an adaptive tissue composed of multiple myofibers that differ in their metabolic and contractile properties including oxidative slow-twitch (type I), mixed oxidative/glycolytic fast-twitch (type Ha) and glycolytic fast-twitch (type Hb) myofibers (Fluck et al., Rev. Physiol. Biochem. Pharmacol., 146:159-216, 2003; Pette and Staron, Microsc. Res. Tech., 50:500-509, 2000). Type I muscle fibers preferentially express enzymes that oxidize fatty acids, contain slow isoforms of contractile proteins and are more resistant to fatigue than are glycolytic muscle fibers (Fluck et al., Rev. Physiol. Biochem. Pharmacol., 146:159-216, 2003; Pette and Staron, Microsc. Res. Tech., 50:500-509, 2000). Type II fibers preferentially metabolize glucose and express the fast isoforms of contractile proteins (Fluck et al., Rev. Physiol. Biochem. Pharmacol, 146:159-216, 2003; Pette and Staron, Microsc. Res. Tech., 50:500-509, 2000).
Endurance exercise training triggers a complex remodeling program in skeletal muscle that progressively enhances performance in athletes such as marathon runners, mountain climbers and cyclists. This involves changes in metabolic programs and structural proteins within the myofibers that alter the energy substrate utilization and contractile properties that act to reduce muscle fatigue (Fluck et al., Rev. Physiol. Biochem. Pharmacol, 146:159-216, 2003; Pette and Staron, Microsc. Res. Tech., 50:500-509, 2000). Training based adaptations in the muscle are linked to increases in the expression of genes involved in the slow-twitch contractile apparatus, mitochondrial respiration and fatty acid oxidation (Holloszy and Coyle, J. Appl. Physiol., 56:831-838, 1984; Booth and Thomason, Physiol. Rev., 71:541-585, 1991; Schmitt et al., Physiol. Genomics, 15:148-157, 2003; Yoshioka et al., FASEB J., 17:1812-1819, 2003; Mahoney et al., FASEB J., 19:1498-1500, 2005; Mahoney and Tarnopolsky, Phys. Med. Rehabil Clin. N. Am., 16:859-873, 2005; Siu at al., J. Appl Physiol, 97:277-285, 2004; Gamier et al., FASEB J., 19:43-52, 2005; Short et al., J. Appl Physiol, 99:95-102, 2005; Timmons et al., FASEB J., 19:750-760, 2005). Such exercise training-related adaptations can improve performance and protect against obesity and related metabolic disorders (Wang at al., P. Biol, 2:e294, 2004; Koves at al., J. Biol. Chem., 280:33588-33598, 2005). Moreover, skeletal muscles rich in oxidative slow-twitch fibers are resistant to muscle wasting (Minnaard et al., Muscle Nerve. 31: 339-48, 2005).